Toxic digoxin-drug interactions: the major role of renal P-glycoprotein.
The clinical use of digoxin is complicated by a large number of drug interactions leading to severe toxicity of the cardiac glycoside. The discovery that digoxin is actively secreted by the renal tubular cell via the p-glycoprotein drug efflux pump has led us to examine whether commonly interacting drugs do so by inhibiting renal tubular secretion of digoxin. We review digoxin-drug interactions which have been studied kinetically in humans, where there are sufficient data on renal clearance of digoxin and GFR.
Koren
G
G
Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada.
Woodland
C
C
Ito
S
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000652:urine; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000889:Anti-Arrhythmia Agents; D017964:Itraconazole; D004077:Digoxin; D016572:Cyclosporine; D014700:Verapamil; D011802:Quinidine